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Renin-angiotensin system blockade improves endothelial dysfunction in hypertension.
1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hypertension (Dallas, Tex. : 1979)
|October 21, 2000
Summary
Angiotensin type 1 receptor antagonists and ACE inhibitors both improve endothelium-derived hyperpolarizing factor (EDHF) responses in hypertensive rats. Combined treatment offers similar benefits to individual therapies, suggesting comparable efficacy in improving vascular function.
Area of Science:
- Cardiovascular Pharmacology
- Vascular Physiology
- Hypertension Research
Background:
- Hypertension is associated with impaired vascular responses mediated by endothelium-derived hyperpolarizing factor (EDHF).
- Angiotensin-converting enzyme (ACE) inhibitors are known to improve EDHF-mediated responses in spontaneously hypertensive rats (SHR).
Purpose of the Study:
- To investigate the effects of an angiotensin type 1 (AT(1)) receptor antagonist on EDHF-mediated responses in SHR.
- To determine if combined AT(1) receptor blockade and ACE inhibition provide additional benefits compared to monotherapy.
Main Methods:
- SHR were treated with an AT(1) receptor antagonist (TCV-116), an ACE inhibitor (enalapril), or both, from 8 to 11 months of age.
- EDHF-mediated hyperpolarization and relaxation to acetylcholine (ACh) were assessed in mesenteric arteries.
- Responses to levcromakalim were also evaluated to assess ATP-sensitive K(+)-channel function.
Main Results:
- All treatments (AT(1) antagonist, ACE inhibitor, or combination) comparably lowered blood pressure in SHR.
- EDHF-mediated hyperpolarization and relaxation to ACh were significantly improved in all treated SHR groups.
- The combination therapy showed a trend towards greater improvement in hyperpolarization in the presence of norepinephrine compared to ACE inhibition alone.
Conclusions:
- AT(1) receptor antagonists are as effective as ACE inhibitors in improving EDHF-mediated vascular responses in SHR.
- Combined AT(1) receptor blockade and ACE inhibition do not appear to offer significant additional benefits over monotherapy for these specific vascular responses.